Table 1.

Emerging therapies targeting lactate metabolism in cancer cells.

Compounds	Mechanisms	T cell functional effects	Impacts on tumor	Ref
Lithium	Block lysosomal acidification Rescue lysosomal diacylglycerol–PKCθ signaling Localize MCT1 to the mitochondrial membrane	Attenuate lactate-induced CD8+ T cell immunosuppression Improve T cell energy utilization	Improve tumor immunosuppression	[57]
Dichloroacetate	Inhibit macrophage ARG1 expression Inhibit IL-23/IL-17 pathway Reduce lactic acid production	Enhance T cell response	Promote anti-tumor immunotherapy	[58, 59]
Dimethyl fumarate	Inhibit GAPDH	Enhance TIL anti-tumor response	Inhibit tumor growth	[60]
Switch-2	Bind to IL-2 receptor subunit IL-2Rα Trigger STAT5 activation	Activate CD8+ T cells	Enhance anti-tumor response	[61]
Gd/CeO2	Oxidize lactic acid; generate -OH Induce mitochondrial damage	Activate CD8+ T cells	Enhance anti-tumor immunity	[62]
APAP-P-NO	Produce large quantities of nitrite S-nitrosylation impair GAPDH activity	Reduce Treg cells Promote CD8+ T cells infiltration	Reverse immunosuppression TME	[63]
HMONs@HCPT-BSA-PEI-CDM-PEG@siMCT-4	Inhibit lactate efflux	Restore T cell activity	Inhibit tumor growth and metastasis	[64]
Sodium lactate	Inhibit histone deacetylase in CD8+ T cells	Increase TCF-1 expression	Promote cancer immunotherapy	[65]